Author affiliations

Citation and License

Arthritis Research & Therapy 2007, 9(Suppl 1):S4
doi:10.1186/ar2168

Published: 29 June 2007

Abstract

Multiple myeloma, a cancer of plasma cells, is associated with excessive tumor-induced,
osteoclast-mediated bone destruction. Hypercalcemia remains the most frequent metabolic
complication of myeloma in patients, and excessive osteolysis plays a major contributory
role in its pathogenesis. The clinical presentation of hypercalcemia in patients varies
depending on the level of ionized calcium; it can be life threatening, as in the case
of hypercalcemic crisis, requiring immediate medical treatment to prevent death. During
the past few years there have been exciting developments in our understanding of the
pathogenesis of myeloma bone disease; in particular, key mediators of the osteoclastic
bone resorption in myeloma have been identified, including receptor activator of nuclear
factor-κB ligand (RANKL) and macrophage inflammatory protein-1α. There is also increasing
evidence that Dickkopf 1, which has been shown to be over-expressed in myeloma patients,
is also a potent stimulator of osteoclast formation and activity. Importantly, the
available data suggest that RANKL is the final common mediator of osteoclastic bone
resorption, irrespective of the upstream initiator molecule. This brief review presents
an overview of the roles played by these mediators in inducing osteolysis in myeloma
bone disease, and it discusses targeting RANKL as a potential new treatment strategy
in myeloma bone disease and myeloma-associated hypercalcemia.